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Flashcards in DM-Table 1 Deck (500):
1

Type 1 DM

requires insulin, autoimmune destruction of pancreatic beta cells

2

Type 2 DM

Progressive, chronically over wt/obese pts, lifestyle modifications, insulin resistance and eventual shut down of beta cells eventually

3

What are some complications of DM?

Emergent hypoglycemia, hyperosmolar hyperglycemic syndrome(HHS-2) or DKA(children-1), microvascular and macrovascular damage, neuropathic damage

4

how does DM present?

polyuria, polydipsia, polyphagia,

5

How do you dx?

If with symptoms-random blood glucose >200mg/dL asymptomatic: fasting bg>=126mg/dLx2, oral glucose tolerance >=200, A1C>=6.5%

6

What is A1C?

Measure of glycosylated hgb- it gives a good idea of glucose control over past 3months

7

What are the 3 levels of A1C and how they differ in therapy?

=9%=Triple therapy(metformin+two other meds)

8

When is metformin contraindicated?

Renal failure, liver or lung disease d/t acidemia(lactic acidosis)

9

Cornerstone of DM2 therapy?

Metformin

10

What are other antihyperglycemic drugs?

Sulfonylureas (hypoglycemia/wt gain), thiazolidinediones (pioglitazone, rosiglitazone-EDEMA-wt neutral), GLP-1 agonist(CI-men2, medullary syndrome- exenatide, liraglutide-secretagogs- wt loss), DPP-4 inhibitors(sitagliptin, linagliptin-protein that increases endogenous GLP-1 preservation=secretagogues- wt neutral)

11

When should secretegogues be discontinued?

S/sx of pancreatitis (nawing back pain-burrowing)

12

What are some ADRs of metformin?

Lacitic acidosis, GI upset

13

What PO anti-hyperglycemic drug causes wt gain?

Sulfonylureas- glipizide, gliburide, chlorpropamide

14

What PO anti-hyperglycemic drug causes water retention?

thiazolidinediones (pioglitazone, rosiglitazone)- don’t use in HF pts

15

What are wt neurtral PO anti-hyperglycemic drugs?

Thiazolidinediones, DPP-4, metformin

16

What subQ anit-hyperglycemic drug causes wt loss?

GLP-1 agonist (exenatide, liraglutide), CI: MEN2 and hx of medullary thyroid cancer

17

Muscle can take up glucose without insulin(T/F)?

True, this is why you should probably not inject insulin before working out…

18

DKA presentations?

Only occurs in type 1 dm, often no previous dx of DM1, s/sx: polyuria,polydipsia, N/V, malaise, fatigue, tachypnea, palpitations, abdominal pain, ALOC(altered conciousness)

19

HHS-hyperosmolar hyperglycemic state

more type 2 dm, older/infirmed or non-compliant patients

20

What is DKA?

Severe insulin deficiency- lipolysis occurs=ketone bodies, acidemia(anion gap will be high),

21

How do you dx DKA?

Clinical and labs: fingerstick glucose>250, UA+dipstick(glucose and ketones), CMP(hyperkalemia(glucose travels with potassium..), hyponatremia, low bicarb, high anion gap), CBC(left shift=infections), ABG(metabolic acidosis), EKG, serum hydroxybutyrate(high=monitor progress)

22

What often times percipitates DKA?

inflammatory process/drug use-cocaine/non-compliance

23

What is PE for DKA?

dry skin, dry mucous membranes, reduced skin turgor, hypotensive, tachycardic, confusion, ill-looking patient

24

What is DKA tx?

ADMIT: Based on ABCs: circulation(depleted fluids)=NS bolus(up to 5L given), administer normal insulin IV(monitor KqH), Hypokalemia(if

25

What are some electrical changes seen on EKG d/t hypokalemia?

Flat T waves, prominant U waves

26

What is the underlying problem with HHS?

Profound dehydration, high glucosuria

27

What is clinical presentation of HHS?

ALOC, focal/global neurologic deficits, thirst polyuria

28

How do you dx HHS?

clinical: fingerstick glucose(>600mg/dl), cmp, ua+ dipstick(high glucose), CBC, CSP, CXR(look for infection), EKG, CT, AZOTEMIA-d/t elevated BUN(less perfusion to kidneys)

29

What is the tx for HHS?

ABC: Replenish fluid volume very first 1-2L of NS in first hr- get serial CMPs qH, once azotemia resolved, can start insulin, monitor K,

30

Hypoglycemia is recognized as?

Sympathetic activation(sweating, tremor, tachycardia, palpitations, anxiety, nausea, vomiting), blurred vision, behavioral changes, fatigue, ALOC

31

What are the normal levels for fasting blood glucose?

70-120mg/dL

32

What is the dawn phenomenon?

increased insulin required in early morning dt GH

33

What is the somogyi effect?

rebound hyperglycemia from night time hypoglycemia.

34

What is the usual insulin to carb ratio?

1:15

35

What is the usual correction factor?

1:50

36

What are rapid acting insulin?

lispro, aspart, apidra

37

what should you do to insulin when adding Pramlintide?

reduce pre-prandial insulin by 50%

38

When should you screen children for DM2?

when BMI over 85th precentil, or wt over 120% of ideal,

39

What is metabolic syndrome?

3 of 5 criteria met (PHAT)

40

What are the ranges for metabolic syndrome?

BP>130/85, HDL cholesterol 102men/>88women, TG>= 150, Fbg >=110

41

What are the characteristics of metabolic syndrome?

impaired lipids, impaired

42

What happens when there is low blood glucose?

Glucagon is released by alpha cells of the pancreas
Liver releases glucose into the blood

43

What happens when there is high blood glucose?

Insulin released by beta cells of the pancreas
Fat cells take in glucose from the blood

44

what are the types of DM?

Type I, II, gestational, other

45

What is the cause of Type I?

Due to B cell destruction, usually leading to absolute insulin def

46

What is Type II caused by?

d/t progressive insulin secretory defect on the background of insulin resistance

47

What are the other types of DM?

Monogenic diabetes- neotnatal, MODY
Dz of endocrine pancreas and drug/chemical induced

48

What is MODY?

Dysregulation of glucose sensing or insulin secretion
AD mutation
Occurs beore 25
Insulin resistance and hypertriacyclglycerolemia absent

49

What causes gestational DM?

Rise in HPL and other hormones that contribute to insulin resistance

50

What is diabetes mellitus?

Metabolic disorder in which carbohydrate metabolism is reduced while that of proteins and lipids in increased

51

How is Diabetes diagnosed?

•Fasting plasma glucose (FPG) ≥ 126mg/dl
OR
•Symptoms of diabetes + casual plasma glucose ≥ 200 mg/dl
OR
•Oral glucose tolerance test (OGTT): 2-h postload glucose ≥ 200 mg/dl

52

What needs to be taken into consideration with A1C?

Need to take into account age, race, anemia or hemoglobin issues

53

What are contraindications to A1C testing?

Use of plasma glucose

54

When should you test for DM?

1)Adults overweight or obese and who have 1 or more additional risk factors for diabetes
2) all pts testing at age 45
3) repeat at a minimum of 3 yr interval if results are normal

55

What are the additional risks for overweight/obese diabetics?

–Physical inactivity
–First degree relative with diabetes
–High risk race/ethnicity (AA, Latino, Native American, Asian American, Pacific Islander)
–Women who delivered a baby weight > 9 pounds or were diagnosed with GDM
–HTN (> 140/90 or on therapy)
–HDL cholesterol 250mg/dL
–Women with Polycysic ovarian syndrome
–A1C > 5.7% on previous testing
–Severe obesity or acanthosis nigricans
–History of CVD

56

When should you test for gestational diabetes?

-Test for undiagnosed diabetes type 2 in pts with risk factors at first prenatal visit
- test at 24-28 wks gestation in women with no hx of dm
-screen women with GDM for persistent DM at 6-12 wk post partum and lifelong screening at least q 3 yrs

57

What is GDM associated with ?

Fetal macrosomia
Higher rate of pre-eclampsia
Mother is at risk for developing type 2

58

What puts women at very high risk for GDM?

Severe obestity, prior hx of GDM or delivery of LGA infants, presence of glycosuria, diagnosis of PCOS, or strong family hx

59

When should women be screened for GDM?

Women at high risk as soon as pregnancy is confirmed
All other at 24-28wks of gestation

60

How is GDM diagnosed?

•Fasting ≥ 95 mg/dL
• 1h ≥ 180 mg/dL
• 2h ≥155 mg/dL
• 3 h ≥ 140 mg/dL
• Women with GDM should be screened for type 2 diabetes 6-12 weeks postpartum

61

What are common comorbid conditions with diabetes?

Depression, OSA, fatty liver dz, CA, fractures, cognitive impairment, low testosterone in men, periodontal dz, and hearing impairment

62

When should you monitor glucose on intensive insulin regimens?

Prior to meals and snacks, occasionally post-prandial, at bedtime, prior to exercise, when they suspect low blood glucose, after treating low blood glucose, and prior to critical tasks

63

When should A1C be monitored?

At least 2x yr in pts that are meeting treatment goals
Quarterly in pts not meeting goals

64

What is the cause of type I diabetes?

Absolute insulin def
Autoimmune destruction of the B cells of the pancreas

65

What markers are present in type I diabetes?

Islet cell antibodies
Autoantibodies to insulin
Autoantibodies to glutamic acid decarboxylase( GAD65)
Autoantibodies to tyrosine phosphates IA-2 and IA-2B

66

What are risk factors for type I DM?

Strong genetic component, environmental factors
White
Other autoimmune disorders

67

What are the 4 main features of the progression of diabetes type I?

1) pre-clinical period with the presence of immune markers
2) hyperglycemia after 80-90% of B cells are destroyed
3) honeymoon phase
4) established disease

68

What is the clinical presentation of hyperglycemia??

Polyuria, polydipsia, polyphagia, wt los, fatigue, infection, blurred vision, poor healing, growth failure in children, N/V

69

What is the tx for type I DM?

Provide exogenous insulin to replace endogenous loss
-insulin
-pramlintide

70

What are the types of insulin?

-rapid acting
-short acting-regular insulin
-intermediate acting- NPH
-long acting-basal insulin

71

What are the rapid acting insulins?

Humalog, novolog, apidra

72

What are the short acting regular insulins?

Novolin, humulin R

73

What are the intermediate acting NPH?

Novolin and humilin N, Neutral protamine Hagedorn (NPH)

74

What are the long acting basal insulins?

Levemir (detemir) and lantus (glargine)

75

What are the high insulin state effects?

-liver: glucose uptake, glycogen synthesis, lipogensis
-muscle: glucose uptake, glucose oxidation, glycogen synthesis, and protein synthesis
-adipose tissue: glucose uptake lipid synthesis and TG uptake

76

What are the low insulin state effects?

-liver: glucose production, glycogenolysis, ketogenesis
-muscle: fatty acid, ketone oxidation, glycogenolysis, proteolysis and amino acid release, NO glucose uptake
-adipose tissue: lipolysis and fatty acid release. NO glucose or TG uptake

77

What is the onset of insulin detemir(levemir)?

Onset 2 hrs

78

What is the peak and duration of insulin detemir?

6 to 9 hrs (blunted)
and 24 hr duration

79

What is the onset, peak, and duration of insulin glargine (lantus)?

Onset 4-5hrs
Peak none or blunted
Duration 22+ hrs

80

What should you do before using NPH?

Roll or invert 10 times

81

What Is the onset, peak, duration of NPH?

Onset of 1-4hrs
Peaks at 6-10hrs
Duration of 12-18 hrs

82

Can NPH also be used as a basal insulin?

Yes if dosed multiple times a day

83

When should short acting regular insulin be injected?

30 min before eating

84

Onset, peak, and duration of short acting regular insulin?

Onset ½- 1 hr
Peak of 2-5 hrs
Duration of 4-6 hrs

85

What insulin most closely mimics the bodys response to glucose absorption?

Rapid-acting insulin

86

When should rapid-acting insulin be injected?

Immediately before eating

87

What is the onset, peak and duration of rapid acting insulin?

Onset: 5-15min
Peak: ½ to 1.5 hrs
Duration: 3.5 -5hrs

88

What is the pre-mixed insulin basal/bolus?

-NPH+regular
70/30
-NPH-like insulin +rapid acting
-aspart protamine/aspart(novolog mix 70/30)
-neutral protamine lispro/lispro (humalog mix 75/25, or 50/50)

89

What is the adverse effect of insulin?

Hypoglycemia- blood glucose

90

What is hypoglycemia a result of?

Decrease of insulin, decreased or delay in meals, increase in exercise

91

What are the S/S of hypoglycemia?

Tremors, palpitation, sweating, excessive hunger, HA, mood changes, irritability, unconsciousness, and seizures

92

How is hypoglycemia tx?

15g of glucose, wait 15min if still

93

What are sources of carbs?

½ cup of juice, 3 graham crackers….liquids are much faster acting

94

What is hypoglycemia unawareness?

Secretion of glucagon and epi are blunted, reducing symptoms of hypoglycemia

95

How does admin affect absorption?

Rate of absorption varied by route and location
IV>IM>SC
Ab>arm>thigh>butt

96

What can pts do to help enhance absorption?

Rub injection site- blood flow enhances

97

How is most insulin stored?

Room temp for up to 28 days

98

What are the exceptions for insulin storage?

–Humalog Mix Pen: 10 days at room temperature
–NPH-Regular Mix Pens : 10 days
–NPH Pens: 14 days
–Novolog Mix Pen: 14 days

99

What does the insulin pump do?

Deliver microliter amounts of insulin continuously as a basal insulin

100

When should the insulin pump be activated?

Before a meal to deliver a bolus

101

What is pramlintide?

Synthetic analog of human amylin, which is co-secreted with insulin from the pancreas in response to a meal

102

What are the 3 primary mechanisms of amylin?

-suppress postprandial glucagon secretion
- regulates the rate of gastric emptying
-reduce food intake

103

Amylin is deficient in which form of diabetes?

Both I and 2

104

What is the primary use of pramlintide?

FDA approved for I/II in pts on optimal insulin therapy who are sill not at goal

105

What is type I dosing for pramlintide?

15mcg SC before meals
meals must be >30g of carbs or >250kcals

106

What do you HAVE to do when starting a pt on pramlitide?

Reduce pre-prandial insulin by 50%

107

What are CI/ precautions with pramlintide?

Gastroparesis, hypoglycemic unawareness, recurrent episodes of hypoglycemia in the last 6 mo, A1C >9%, poor adherence to insulin or self monitoring

108

What is the black box warning for pramlintide?

Hypoglycemia
Usually within 3 hrs of injection
This is why you have to reduce preprandial insulin by 50% at initiation

109

What are other adverse effects of pramlintide?

Nausea, drug interactions, and delayed gastric emptying

110

What are the ADA guidelines for glycemic control of TypeI/II?

•A1C

111

What are steps for recommended therapy in diabetes type I?

1. Use of multiple dose insulin injections
–3-4 injections/day of basal and prandial insulin
2. Matching prandial insulin to:
–Carbohydrate intake
–Premeal BG
–And anticipated activity
3. Use of insulin analogs as prandial insulin

112

What is the standard of care in type I diabetes?

-miminum of 4 injections
-basal admin once/day typically at bedtime
-rapid acting bolus given just before meals

113

What is initial insulin dosing based off of?

Weight

114

What is the max insulin units that can be absorbed or injected at one site?

50 units

115

What are the 2 parts to prandial insulin dosing?

1. insulin to carb ration (I:C)
2. correction factor

116

What is the typical starting I:C?

1:15
1 unit of insulin covers 15 g of carbs

117

What is correction factor?

Number of mg/dL the blood glucose will drop after injecting 1 unit of rapid-acting or regular insulin

118

What is a typical starting CF dose?

1:50
1 unit of insulin for every 50 mg/dL above 100

119

What is the 1500 rule using TDD to calculate the CF?

1500/TDD mg/dL the blood glucose will drop after 1 unit of insulin

120

What are causes of fasting hyperglycemia?

Dawn phenomenon: increased insulin requirement late in the sleep cycle- nocturnal hyperglycemia
Somogyi phenomenon: nocturnal hypoglycemia followed by rebound hyperglycemia

121

When does the somogyi effect more often happen?

When intermediate insulins are used with dinner

122

How does the somogyi effect happen?

Happens when hypoglycemia causes the release of counterregularoty hormones hich stimulate hepatic glucose production which leads to rebound hypergycemia

123

When should you measure blood glucose levels of suspecting somogyi effect?

Btwn 2 and 4 am then again at 7am
–If they are 180-200 mg/dL rebound hyperglycemia may have occurred

124

What is the dawn phenomenon?

An increased insulin requirement in the early morning
About 1-3am d/t a surge of growth hormone relsease

125

What is the cause of postprandial hyperglycemia (>180)? When does it occur? How is it treated?

Not enough insulin given with the meal
Happens 1-2 hrs after eating
Increase the pre-meal insulin dose

126

How should the I:C be adjusted if the post prandial glucose is consistently >180?

Adjust by 2-5 grams of carbs

127

How should the I:C be adjusted if it is at 1:15 and the 2hr post prandial blood glucose levels are 210?

Increase to 1:12

128

What are strategies to avoid hypoglycemia?

-planned exercise: decrease pre-prandial insulin dose before the exercise
-unplanned exercise: consume an additional 15-30g of carbs for each 30 min of exercise
-might need to decrease pre-prandial insulin dose for the meal after exercising

129

What should you always check during illness if your blood glucose is consistently over 240?

Urine ketones!
(persistent is early sign of DKA)

130

What are complications of DM I?

Hypoglycemia
Ketoacidosis

131

What are s/s of ketoacidosis?

–Develop rapidly
–Fruity or acetone breath
–N+V
–Dehydration- typically 6L or more
–Polyuria
–Polydipsia
–Deep, rapid breathing
Lethargy, HA, weakness

132

What is the diagnostic criteria for ketoacidosis?

–Hyperglycemia (> 250mg/dL)
–Ketosis (anion gap > 10)
–Acidosis (arterial pH

133

How is DKA tx?

Reverse underlying metabolic abnormality
Rehydrate with NS at 1L/hr
Normalize serum glucose with regular insulin at 0.1-0.2 unit/kg/hr by CI

134

What is the pathophys of DM II?

Insulin resistance and relative insulin def

135

What are the other physiologic issues that happen in Type II DM?

Reduced circulating levels of GLP-1
Loss of first phase insulin response post meal
Loss of amylin

136

What are risk factors for type II?

-Physically inactive
-1st degree relative with diabetes
-Minority ethnic groups
-Gestational diabetes or delivering baby >9 lbs
-Hypertension
-HLD 250 mg/dL
-Polycystic ovary syndrome
-Previous impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)
-History of vascular disease
-Psychiatric illness

137

When should you consider screening for DM?

Pts of any age if their BMI >/= 25kg.mg and they have additional risk factors for DM
If NO risk factors begin at age 45

138

How often should screening be repeated?

Q 3 yrs

139

What indicate screening for type 2 DM in kiddos?

Overweight: BMI >85th percentile for age and sex, wt for height >85th percentile, or weight >120% of ideal for height
PLUS 2 of the following
Fhx in 1st or 2nd degree relative, ot white, signs of insulin resistance, GDM

140

When should testing in kiddos be done?

Start at 10 or onset of puberty
Test FPG q 2yrs

141

What is the definition of pre-DM?

IFG= 100-125
IGT= 2hr post load glucose 140-199

142

IFG and IGT indicate risk factor for what?

Diabetes and CV disease

143

What is diagnostic for DM II?

FPG >/= 126mg/dL
OR
Symptoms of diabetes + casual plasma glucose >/= 200 mg/dL
OR
Oral glucose tolerance test (OGTT):
2hr-postload glucose >/= 200 mg/dL
A1C>/= 6.5

144

What is the preferred test for diagnosing DM?

FPG./= 126mg/dL

145

What are the 3 major metabolic abnormalities that contribute to hyperglycemia?

-Defective glucose-induced insulin secretion
-Increased hepatic glucose output
-Inability of insulin to stimulate glucose uptake in peripheral target tissues.

146

What are some other causes of insulin resistance?

Cushings- excessive corticosteroids
Acromegaly- excessive GH
PCOS

147

What are the microvascular complications of DM?

Retinopathy, nephropathy, neuropathy

148

What are the macrovascular complications of DM?

Atherosclerotic CV diagnosis, dyslipidemia

149

What is the A1C goal for adults in general? Why?

150

What are some ways to prevent DM in pts with IGT or IFG?

Wt loss of 7% body weight and increase PE to 150 min/week
Add 14g of dietary fiber/ 1000 kcal
Meds

151

What drugs have been studied for prevention of DM?

Metformin, rosiglitazone, acarbose, troglitazone, orlistat

152

How can DM be clinically managed?

Diet/ exercise are cornerstones of DM management regardless of severity and symptoms
Meds highly individualized

153

What is the goal in clinical management of DM?

To improve symptoms of hyperglycemia, reduce onset & progression of microvascular and macrovascular complications, reduce mortality & improve QOL.

154

What are some ways to improve sugars and manage CV risk factors?

Smoking cessation, lipid management, BP control, and antiplatelet therapy

155

How often should glucose be self monitored?

If insulin injection: at least 3x/day
If oral: use to achieve glycemic goals

156

How often should A1C be monitored?

At least 2x yearly in pts at goal
Q 3 mo in pts who aren’t meeting goals or who have had a change in meds

157

What are the oral therapy options for DM II?

Biguanides- Metformin
Secretagogues- sulfonylureas
Short acting secretagogues- meglitinides
Insulin sensitizers- TZD, thiazolidinediones
Alpha-glucosidase inhibs
Dipeptidyl peptidase-4( DPP-4)inhib
Bile acid sequestrants
Colesevelam (welchol)
D2 agonists- bromocriptine
Sodium glucose transporter 2 inhib( SGLT2 inhib)- canaglifozin, dapagliflozin, empagliflozin

158

What is the MOA of metformin?

Decreases: production of hepatic glucose production, intestinal glucose absorption
Increases: peripheral glucose uptake and insulin sensitivity

159

What are the clinical used of metformin?

Works best in pts with significant hyperglycemia
First line in type 2 DM pharm tx
Shown to decrease CVD in DM

160

What are the ADRs of metformin?

GI- diarrhea, ab bloating, nausea
Vit B12 def
Lactic acidosis

161

How can GI affects be minimized?

Take with food, titrate dose at weekly intervals to minimize

162

What is an ADR of metformin that is actually beneficial?

Hypoglycemia

163

What needs to be monitored and when if your pt is taking metformin?

SCr at baseline
FPG at 2 weeks
A1C at 3 mo

164

What is the pathophys behind metformin associated lactic acidosis?

Increased production of lactate n the intestine leads to increased portal lactate concentrations which decreases liver pH, decreasing lactate metabolism and leads to accumulation in the blood

165

What are CI with metformin?

Renal impairments, acute or chronic metabolic acidosis

166

What are the precautions of metformin?

Radiocontrast studies, age>80 unless normal GFR, hypoxic states, alcoholism, heart failure requiring pharm tx

167

What are some benefits of metformin?

- no weight gain
- no hypoglycemia as a monotherapy
- inexpensive
- approved an monotherapy and a combo therapy

168

What is the MOA of sulfonylureas?

Direct stimulation of insulin release from viable pancreatic beta-cells thus reducing blood glucose levels
Blocks ATP-sensitive K+ channels, resulting in depolarization and Ca++ influxrelease of insulin

169

Which generation of sulfonylureas are no longer used?

Generation 1 because of the higher risk of hypoglycemia

170

What are the 2nd generation sulfonylureas?

Glyburide, Glipizide, Glimepiride, Gliclazide

171

What are the clinical used of 2nd generation sulfonylureas?

Mild to moderate Type 2 diabetes

172

What are the ADRs of 2nd gen sulfonlyureas?

Hypoglycemia, weight gain, muscular weakness, dizziness, confusion, skin rash, photosensitivity, blood dyscrasias, cholestatic jaundice

173

What are the specific directions or risks with glyburide?

Admin with breakfast or first main meal
Greater risk of hypoglycemia d/t longer half life
Don’t use if CrCl

174

What are directions and risks with Glipizide?

-Administer 30 min before first main meal
-Not recommended if CrCl

175

What are specifics for Glimepiride?

-Administer with first main meal
-Not recommended if CrCl

176

What affects the absorption of sulfon?

Reduced GI absorption if blood glucose is >250mg/dL

177

What needs to monitored if your pt is on sulfonylureas?

FGP- 2 weeks
A1C- in 3 mo

178

What are CI/ cautions for sulfonylureas?

Cross sensitivity to sulfa, higher risk with hypoglycemia in pts with renal or hepatic dz, avoid with ETOH, CI in pregnancy since it can cross the placenta

179

What are the drug interactions with sulfonylureas? what are they doing?

May potentiate hypoglycemia via reduced hepatic metabolism, decreased urinary excretion or displacement from plasma proteins
-Sulfonamide antibacterials
-Propranolol
-Salicylates
-Phenylbutazone
-ETOH

180

What is the MOA of the short acting secretagogues (meglitinides)?

Stimulate insulin release from pancreatic beta cells- increases insulin secretion

181

When should meglitinides be taken?

With meals to target postprandial glucose levels

182

What are the meglitinides?

Repaglinide and nateglinide

183

What is repaglinide approved for?

Monotherapy or with metformin

184

When should repagalinide be given?

Taken before meals 3x daily

185

What is nateglinide approved for?

Monotherapy or combo with metformin

186

What is the difference with nat and rep?

Nate has a faster onset of action and shorter duration of action than rep, less A1C reduction than rep
Also take 3x daily before meals

187

What are the ADRs of meglitinides?

Hypoglycemia and weight gain

188

What do you need to be monitoring if your pt is on meglitinides?

FGP at 2 weeks
Postprandial glucose at initiation
A1C at 3 months

189

What are the TZDs?

Rosiglitazone and pioglitazone

190

What is the MOA of TZDs?

regulate glucose metabolism resulting in increased insulin sensitivity in adipose, liver and skeletal muscle
they REQUIRE INSULIN for action

191

Whats shouldn’t you give with rosiglitazone?

Exogenous insulin! Will lead to edema

192

About how long does it take for the biological effect of TDZs to be seens?

4 weeks

193

What are the CV effects of pioglitazone?

HDL; triglycerides = decreased CVD

194

What are the CV effects of rosiglitazone?

: LDL(not so great) and HLD

195

What are the ADRs of the TZDs?

Fluid retention and peripheral edema, weight gain, new onset heart failure, bone fractures, increased risk of MI

196

What are the CI of TDZs?

Alcohol abuse, elevated liver enzymes, hepatotoxicity, hepatic dz, and HF in class III or IV

197

What are the black box warnings for the TDZs?

Both: CHF
Ros: MI risk

198

What are the alpha- glucosidase inhibitors?

Acarbose and miglitol

199

What do the alpha-glucosidase inhibitors do?

Delay intestinal carb absorption
Prevents glucose absorption and decreases post-prandial glucose levels

200

Is there a risk for hypoglycemia with Alpha Glucosidase inhibitors?

Nope

201

What are the ADR of the alpha glucosidase inhibs?

Not well tolerated
GI- loose stool, flatulence, abdominal cramping
Bonus: NO WT GAIN

202

How can you minimize GI effects of the alpha-gs?

Starting low and increase slowly
Curtailment of carb consumption

203

What are the CI for alpha-gs?

Chronic intestinal dz and cirrhosis

204

What needs to be monitored if your pt is on alpha gs?

Post prandial glucose at initiation and A1C in 3 months

205

What are the DPP-4 inhibitors?

Sitagliptin, saxagliptin, algoliptin, linagliptin, and vildagliptin

206

What is the MOA of the DPP-4 inhibitors?

Prevent the egredation of endogenous glucagon like peptide 1 and insulinotropic polypeptide
Results in increased insulin release and decreased glucagon levels in circulation in glucose dependent manner

207

When does the dosage of DPP-4 inhibs need to be adjusted?

CrCl

208

What are the ADRs of DPP-4 inhibs?

HA and UTI
Generally well tolerated
Investigated for pancreatic toxicity and increase in heart failure

209

What should you be monitoring if your pt is on DPP-4 inhibs?

Renal fxn
A1C in 3 mo

210

What is the bile acid sequestrant?

Colesevelam (welchol)

211

What is the moa of colvesevelam?

bind bile acid in intestinal tract, increasing hepatic bile acid production- possibly decrease hepatic glucose production and increase incretin levels

212

Is colvesevelam used as a monotherapy?

No

213

What are the ADRs of colvesevelam?

Constipation/nausea/indigestion
triglycerides
May decrease absorption of other medications

214

What are the CI of colvesevelam?

Bowel obstruction
History of hypertriglyceridemia-induced pancreatitis
Triglycerides >500 mg/dL

215

What is the D2 agonist?

Bromocriptine

216

What is the MOA of bromocriptine?

activate dopamine receptors, modulate hypothalmic regulation of metabolism, increase insulin sensitivity

217

What are the benefits of bromocriptine?

No hypoglycemia and decreased CVD

218

What are the ADRs of bromocriptine?

Dizzy/syncope, V, fatigue, rhinitis

219

What are the SGLT2 inhibitors?

Canagliflozin, dapagliflozin, empagliflozin

220

What is the MOA of SGLT 2 inhibs?

Inhibits SGLT2 in proximal nephron; Reduces reabsorption of filtered glucose thereby increasing urinary excretion of glucose

221

What are the benefits of SGLT2 inhibs?

No hypoglycemia, decreased weight, decreased BP

222

What stage of DM are SGLT2 inhibs effective at?

All the stages
Mono or adjunct therapy

223

What are the ADRs of SGLT2 inhibs?

Increased potassium, renal insufficiency (with baseline GFR

224

What do you need to make sure is corrected prior to initiating SGLT2 inhib tx?

Correct any volume depletion!
Not for pts with GFR

225

What are the non oral therapies for DM II?

GLP-1 agonists, pramlintide or symlin, and insulin

226

What are the GLP-1 agonists?

Exenatide, Liraglutide, Albiglutide, Lixisenatide, Dulaglutide

227

What is the MOA of GLP-1 agonists?

Increase insulin secretion(glucose dependant), decrease glucagon secretion, slows gastric emptying, increase satiety

228

What are GLP-1 agonists resistant to?

Degredation by DPP-4

229

What is the FDA approved use for GLP-1 agonists?

Type 2 DM in pts on metformin, sulfonylurea, TZD, or a combo who are not at goal

230

What are GLP-1 agonists NOT approved for?

Use with basal insulin

231

What are the ADRs of GLP-1 agonists?

-N/V/D (30-45%)
-Increase Heart Rate
-Acute Pancreatitis-possibly
-SQ injection
-Anti-exenatide antibodies

232

What are the precautions of GLP-1s?

-ClCr

233

What are the benefits of GLP-1?

-No hypoglycemia
-Modest weight loss
-Decrease of some cardiovascular risk factors

234

What should you monitor in a pt who is on GLP-1 tx?

Renal fxn and A1C in 3 mo

235

What is pramlintide approved for?

Type I/II DM in pts on optimal insulin therapy who are still not at goal
Can be with or without metformin and or sulfon tx

236

When should pramlintide be administered?

In conjunction with mealtime insulin

237

What are the the 2 pens and their dosages for pramlintide?

-SymlinPen 60: for doses of 15, 30, 45 or 60 mcg
-SymlinPen 120: for doses of 60 or 120 mcg

238

If your pt has type II DM and HTN, how should you control their HTN?

ACEI or ARB, potential combo with a thiazide
Diet and lifestyle

239

When should you screen your DM pts for dyslipidemia?

At DM initial evaluation and or at age 40 and q 1-2 yrs after

240

What is the first choice for lowering LDL in your DM pts?

Statin

241

When should a stain and lifestyle be added regardless of the lipid levels of your DM pt?

-Overt CVD
-Without CVD who are over the age of 40 and have one or more other CVD risk factors
-In pts whose LDL goal can’t be achieved, a 30-40% reduction is acceptable

242

If you pt has DM and CHD, how should they be tx?

Daily ASA unless CI

243

What is hyperosmolar hyperglycemia state?

HHS- life threatening condition similar to DKA
Extreme hyperglycemia and fluid deficits that arises from inadequate insulin but occurs primarily in older type II DM pts

244

What does HHS lack?

Lipolysis, ketonemia, and acidosis

245

What pts are at greatest risk for developing HHS?

Hyperglycemia and dehydration lasting days to weeks

246

What is the diagnostic criteria for HHS?

-Plasma glucose > 600mg/dL
-Serum osmolality of > 320 mOsm/kg

247

How is HHS tx?

-Rehydration
-Correction of electrolyte imbalances
-Continuous insulin infusion

248

What are the 3 hormones secreted by the thyroid gland?

T3-triiodothyronine
T4- thyroxine
Calcitonin

249

What is required for hormones synthesis?

Iodine

250

Which hormone is more potent?

T3

251

How is t3 produced?

Majority is produced from the peripheral conversion of T3-T4

252

What inhibits the conversion to T3?

BBlockers, corticosteroids, and amiodarone

253

What stimulates the pituitary to syntesize and release TSH? thyrotropin-releasing hormones?

thyrotropin-releasing hormone TRH, from the hypothalamus

254

What can block the transport of iodide into thyroid?

Bromide, fluoride and lithium

255

What can impair the coupling of thyroid hormones?

Sulfonylureas and thionamides

256

Thyroid hormones are released following what?

Proteolytic cleavage from the thyroglobulin

257

What can block this release?

High levels of iodine or lithium

258

What is free T4 level used to evaluate?

Free levels in euthyroid sick pts

259

What does sensitive TSH valuate? When it is increased? Decreased?

Evaluates the pituitary negative feedback system
Increased: primary hypo
Decreased: primary hyper

260

What is the definition of sub clinical hypothyroidism?

Serum TSH concentration above statistically defined upper limit of reference range

261

What is it measured by?

Serum free thyroxine within reference range

262

What are effects of hypothyroidism?

Increased risk of CHD
—Systolic Dysfunction
—Reduced stress tolerance during exercise
—Cardiac autonomic dysfunction
—Reduced oxygen uptake during exercise
—Diastolic hypertension
—Increased arterial stiffness
—Pro-atherosclerotic profile
—Insulin resistance
—Pro-coagulative pattern
—Decreased activity
◦Von Willebrand factor
◦Factor VIII

increase risk for placental abruption and preterm delivery

263

What are the s/s of hypothyroidism?

◦Tiredness
◦Lethargy, Muscle pains
◦Weight gain
◦Intolerance to cold
◦Dry skin, Coarse skin
◦Bradycardia
◦Mental impairment
◦Dry thinning hair

264

What effect does hypothyroidism have on certain drugs?

-digitalis: decreases volume of distribution
-insulin: impaired degradation
-warfarin: delayed catabolism of clotting factors

265

What are causes of primary hypothyroidism?

◦Hashimoto’s Disease
◦Iatrogenic hypothyroidism-radioactive iodine ingestion, post thyroidectomy
Iodine deficiency

266

What are common causes of secondary hypothyroidism?

Pituitary dz and hypothalamic dz

267

What type of pts are at increased risk for hypothyroidism?

◦Postpartum women
◦Family history of autoimmune thyroid disorders
◦Patients with previous head and neck of thyroid irradiation or surgery
Other autoimmune endocrine
Non-autoimmune: celiac disease, vitiligo, MS, pernicious anemia, Down’s syndrome

268

What are the s/s of hypothyroidism in elderly pts?

◦Hoarseness
◦Deafness
◦Confusion
◦Dementia
◦Ataxia
◦Depression
◦Dry skin
◦Hair loss

269

What is the most common cause of hypothyroidism?

Hashimotos thyroiditis

270

What is Hashimotos thyroiditis ?

An autoimmune disease resulting in fibrosis of the thyroid gland, antibodies to TSH receptor

271

What does congenital hypothyroidism result in?

dwarfism and mental retardation (cretinism)

272

What is myxedema?

When pts appear to have edema under the skin-most severe form of hypothyroidism

273

What are the clinical features of myxedema?

◦Hypothermia
◦Advanced hypothyroid symptoms
Altered sensorium

274

What can myxedema lead to?

Myxedema coma- high mortality rates

275

What is the drug of choice for hypothyroidism management?

levothyroxine

276

What is the MOA of levothyroxine?

Isomer of T4 is converted to T3

277

What are the ADRs of levothyroxine?

◦Arrhythmias
◦Tachycardia
◦Anginal pain
◦Cramps
◦HA
◦Restlessness
◦Sweating
◦Weight loss
◦Osteoporosis

278

What is the CI for levothyroxine?

Thyrotoxicosis

279

What how often do you need to be monitoring your pt if taking levthyroxine?

◦Every 6-8 weeks until TSH normalized, then every 6-12 months
◦If doses changed, recheck TSH in 2-3 months

280

Levothyroxine has many drug interactions. What does it alter absorption of?

◦Cholestyramine
◦Ferrous sulfate
◦Sucralfate
Aluminum hydroxide

281

Levothyroxine has many drug interactions. What does it incease the metabolism of?

◦Rifampin
◦Phenytoin
◦Carbamazepine

282

What is the effect of oral contraceptives or estrogen with levo?

◦Increase thyroid binding globulin, resulting in lower free thyroid hormone

283

What is the effect of lithium with levo?

◦Inhibits synthesis and release of thyroid hormone

284

What is the effect of amiodarone with levo?

Block conversion T4 to T3

285

What is the effect of warfarin with levo?

Increases metabolism of clotting factors

286

What are the other 2 drug choices for hypothyroidism management?

Liothyronine sodium and liotrix

287

Why is liothyronine generally not used for maintenance?

therapy because of its short half-life and duration of action.

288

What are the indications for liothyronine?

–Initial therapy of myxedema (skin disorder) and myxedema coma
–Short-term suppression of TSH in patients undergoing surgery for thyroid cancer.
–Patients w/5’-deiodinase deficiency who cannot convert T4 to T3.

289

Is liotrix any more effective than levo?

No

290

What is the specific tx regime for myxedema coma?

◦IV bolus levothyroxine 300-500mcg
◦Maintenance 75-100 mcg IV until able to switch to PO
◦IV hydrocortisone 100mg q 8h until coexisting adrenal suppression is ruled out
◦Supportive therapy- ventillation, euglycemia, blood pressure, body temp maintained

291

What is the specific tx for congenital hypothyroidism?

◦Initial therapy within 45 days of birth at 10-15mcg/kg/d, associated with improved IQ’s in treated infants
◦Dose progressively decreased to typical adult dose beginning 11-20 years
- aggressive tx important for normal development!

292

How is hypothyroidism tx in pregnancy?

—Treatment: levothyroxine
◦20% requires dose increase during pregnancy/ decrease after
◦Typically require 36 mcg/day increase in dosage

293

What causes hyperthyroidism?

◦Overproduction of endogenous hormone
◦Exposure to excess endogenous hormone
◦Elevated free and total T3, T4 or both serum concentrations

294

What are the subclinical and clinical serum levels of TSH for diagnosis?

—Subclinical
◦TSH 13.2 mcg/dL

295

What are S/S of hyperthyroidism?

◦Nervousness
◦Anxiety
◦Palpitations
◦Increased basal metabolic rate (BMR)
◦Weight loss
◦Increased appetite
◦Increased body temp (heat intolerance)
◦Sweating
◦Fine Tremor
◦Tachycardia
◦Classical ophthalmic signs

296

What is the most common cause of hyperthyroidism?

Graves dz

297

What is graves dz?

Autoimmune syndrome that includes hyperthyroidism, diffuse thyroid enlargement, myxedema, thyroid acropachy

298

What forms against the thyroid cell?

IgG antibodies bind and activate the receptor

299

Why is TSH undetectable in graves?

From the negative feedback from elevated thyroid hormone- disproportionate increase in T3 compared to T4

300

What is the most common cause of hyperthyroidism in preggo?

Graves
Inappropriate production of hCG can cause subclinical or overt hyperthyroidism

301

What are common complications if hyperthyroidism is left untreated in the preggos?

◦Spontaneous abortion
◦Premature delivery
◦Low birth weight
◦Eclampsia

302

What is the drug of choice for tx graves in preggo?

PTU at the lowest effective dose

303

What is a thyroid storm?

Life threatening medical emergency characterized by ◦Severe thyrotoxicosis, high fever (often > 103 F), tachycardia, tachypnea, dehydration, delirium-coma, N/V, and diarrhea

304

What are the precipitating factors to a thyroid storm?

◦Infection, trauma, surgery radioactive iodine treatment, withdrawl from antithyroid drugs

305

How can you tx a thyroid storm?

◦Suppression of thyroid hormone formation and secretion
◦Anti-adrenergic therapy
◦Administration corticosteroids
◦Treatment of complications

306

What are the pharmacologic options for hyperthyroidism?

Thioamides, Iodines and iodine containing agents. Radioiodine, Lithium carbonate, Beta adrenergic antagonists, corticosteroids

307

What are the thioamides?

PTU- propylthiouracil
MMI- methimazole

308

What is the MOA of the thioamides?

Block thyroid hormone synthesis
PTU also inhibits DI which deiodinates peripheral T4 to T3

309

What are the indications for the thioamides?

◦Management of hyperthyroidism
◦Thyrotoxic crisis
◦In the preparation of patients for surgical subtotal thyroidectomy

310

Why might MMI be preferred?

Generally has fewer side effect and is 10x more potent than PTU, meaning it requires lower dosages

311

What are the most frequent ADRs of thioamides?

–Rash
–Arthralgia
–Myalgia
–Cholestatic jaundice
–Lymphadenopathy
–Drug fever
–Psychosis
–Alopecia

312

What are the most serious ADRs of the thioamides? When do they typically happen?

Within first 3 mo of therapy
–Arganulocytosis-must obtain baseline white blood cell count (stop if develop fever or sore throat)
–Hepatotoxicity-baseline white blood cell count (stop if pt. develops fever or sore throat)
–Vasculitis-drug induced lupus or anti-neutrophil

313

What can thioamides cause in excessive amounts over long periods of time?

Hypothyroidism and enlargement of the thyroid gland

314

What are indications for the iodines and iodine containing agents?

◦Preoperatively for thyroidectomy (7-14 days)
◦Used after RAI (3-7 days), to allow RAI to concentrate in thyroid

315

What are the CI for iodines?

Should not be given to breastfeeding women- can cause goiter in infants

316

How are the iodines administered?

Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole

317

Should you give iodines long term?

No- they loose effectiveness

318

What are the ADRs of the iodines?

◦Hypersensitivity rxn
◦HA
◦Lacrimation
◦Conjunctivitis
◦Laryngitis
◦Thyrotoxicosis in patients w/nontoxic goiter
◦Drug fever
◦Acneform rash
◦Metallic taste in mouth

319

When is radioiodine used?

For thyroid ablation in the management of hyperthyroidism

320

When is radioiodine the agent of choice?

Graves, toxic autonomous nodules, toxic multinodular goiters

321

What is the goal of radioiodine? MOA?

To destroy overactive thyroid cells
◦Taken up by other organs- organification only in thyroid
◦The ablative effect is exerted primarily through beta-particle emissions, which destroy thyroid tissue.

322

What is the major disadvantage to using radioiodine?

◦Hypothyroidism in most patients
◦Can not be used in pregnancy
◦Hypothyroid often occurs months-years after RAI
◦African Americans are most likely to be resistant to RAI (require multiple doses)

323

What is the MOA of lithium carbonate?

◦Lithium inhibits thyroidal incorporation of I- into thyroid gland which inhibits the secretion of thyroid hormones from follicular cells

324

What are the indications for lithium carbonate?

Offers no advantage over thioamide
Can be used for temporary control of thyrotoxicosis in pts allergic to thioamides and iodine

325

When are beta-adrenergic antagonists used in hyperthyroidism?

to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance

326

Is it a primary or adjunct therapy?

Adjunct! No effect on peripheral thyrotixicosis and therapeutic effect

327

Which corticosteroids can be used in hyperthyroidism?

—Dexamethasone
—Prednisone
—Methylprednisolone
—Hyrocortisone

328

What are the effects of the corticosteroids?

◦Decreases thyroid action
◦Decreases immune response in Grave’s disease
reduce T3

329

When are corticosteroids useful?

Thyroiditis and thyroid storm

330

When is a thyroidectomy indicated?

large glands, severe ophthalmopathy, lack of remission on treatment

331

What pts should not have a thyroidectomy?

On pts with low RAI uptake

332

What medications should the pt be on before during and after the surgery?

—Propylthiouracil (PTU) or methimazole (MMI) until pt is euthyroid (6-8 weeks) followed by iodide 500 mg/day x 10-14 days
—Beta blocker (propranolol/ nadolol) pre- and post-surgery to maintain HR

333

What are complications of a thyroidectomy?

◦Hyperthyroidism
◦Hypothyroidism
◦Hypoparathyroidism
◦Vocal cord abnormalities

334

What are drugs your pt may be taking that if you added a thyroid or antithyroid agent would have interactions?

◦Warfarin
◦Lithium
◦Diabetes medication requirements may change
◦Potassium iodide used as expectorants
◦Cardiac glycosides such as digoxin may require dosage adjustments
◦Amiodarone
CNS depressants

335

Amiodarone and iodinated contrast media can inhibit conversion of T4 to T3 in peripheral circulation and the pituitary gland. What are the levels and when do these happen?

–Iodinated Contrast
‭ ‬Reduction in levels in week 1
‭ ‬Return to normal by week 2
–Amiodarone
‭ ‬Transient elevation in TSH during first 3 months
‭ ‬Persistent FT4 elevations and reduced T3 in on-going therapy

336

What prescription drugs containing iodides can induce thyroid dz?

–Amiodarone
–Radiocontrast dye
–Povidone iodine
–Iodinated glycerol

337

What non-prescription drugs containing iodides can induce thyroid dz?

–Cough and cold
–Kelp
–Herbals
–Dietary supplements/ weight loss products

338

What is iodine induced hyperthyroidism called?

Jod-basedow dz

339

When does jod-b develop and how is it tx?

◦Develops within 3-8 weeks after exposure in up to 5% pts
◦Treatment with thioamides and beta blockers

340

What pts are at risk of developing iodine induced hypothyroidism?

Pts being tx with Amiodarone

341

How is iodine induced hypothyroidism tx?

levothyroxine replacement

342

What other drug can induce hypothyroidism? How is this tx?

Lithium- more like if tx >2ys
Tx: levo to reverse
◦Can spontaneously resolve without treatment
◦Stopping lithium does not always resolve symptoms or goiter
◦May require surgical intervention

343

When might interferon alpha induced thyroid dz present?

within 6-8 weeks of starting therapy or occur 6-23 months after start

344

How is IFNa induced dz tx?

Hypothyroidism resolves spontaneously within 2-3 months after stopping therapy in most patients- may take longer

345

What are the 3 hormones secreted by the thyroid gland?

T3-triiodothyronine
T4- thyroxine
Calcitonin

346

What is required for hormones synthesis?

Iodine

347

Which hormone is more potent?

T3

348

How is t3 produced?

Majority is produced from the peripheral conversion of T3-T4

349

What inhibits the conversion to T3?

BBlockers, corticosteroids, and amiodarone

350

What stimulates the pituitary to syntesize and release TSH? thyrotropin-releasing hormones?

thyrotropin-releasing hormone TRH, from the hypothalamus

351

What can block the transport of iodide into thyroid?

Bromide, fluoride and lithium

352

What can impair the coupling of thyroid hormones?

Sulfonylureas and thionamides

353

Thyroid hormones are released following what?

Proteolytic cleavage from the thyroglobulin

354

What can block this release?

High levels of iodine or lithium

355

What is free T4 level used to evaluate?

Free levels in euthyroid sick pts

356

What does sensitive TSH valuate? When it is increased? Decreased?

Evaluates the pituitary negative feedback system
Increased: primary hypo
Decreased: primary hyper

357

What is the definition of sub clinical hypothyroidism?

Serum TSH concentration above statistically defined upper limit of reference range

358

What is it measured by?

Serum free thyroxine within reference range

359

What are effects of hypothyroidism?

Increased risk of CHD
—Systolic Dysfunction
—Reduced stress tolerance during exercise
—Cardiac autonomic dysfunction
—Reduced oxygen uptake during exercise
—Diastolic hypertension
—Increased arterial stiffness
—Pro-atherosclerotic profile
—Insulin resistance
—Pro-coagulative pattern
—Decreased activity
◦Von Willebrand factor
◦Factor VIII

increase risk for placental abruption and preterm delivery

360

What are the s/s of hypothyroidism?

◦Tiredness
◦Lethargy, Muscle pains
◦Weight gain
◦Intolerance to cold
◦Dry skin, Coarse skin
◦Bradycardia
◦Mental impairment
◦Dry thinning hair

361

What effect does hypothyroidism have on certain drugs?

-digitalis: decreases volume of distribution
-insulin: impaired degradation
-warfarin: delayed catabolism of clotting factors

362

What are causes of primary hypothyroidism?

◦Hashimoto’s Disease
◦Iatrogenic hypothyroidism-radioactive iodine ingestion, post thyroidectomy
Iodine deficiency

363

What are common causes of secondary hypothyroidism?

Pituitary dz and hypothalamic dz

364

What type of pts are at increased risk for hypothyroidism?

◦Postpartum women
◦Family history of autoimmune thyroid disorders
◦Patients with previous head and neck of thyroid irradiation or surgery
Other autoimmune endocrine
Non-autoimmune: celiac disease, vitiligo, MS, pernicious anemia, Down’s syndrome

365

What are the s/s of hypothyroidism in elderly pts?

◦Hoarseness
◦Deafness
◦Confusion
◦Dementia
◦Ataxia
◦Depression
◦Dry skin
◦Hair loss

366

What is the most common cause of hypothyroidism?

Hashimotos thyroiditis

367

What is Hashimotos thyroiditis ?

An autoimmune disease resulting in fibrosis of the thyroid gland, antibodies to TSH receptor

368

What does congenital hypothyroidism result in?

dwarfism and mental retardation (cretinism)

369

What is myxedema?

When pts appear to have edema under the skin-most severe form of hypothyroidism

370

What are the clinical features of myxedema?

◦Hypothermia
◦Advanced hypothyroid symptoms
Altered sensorium

371

What can myxedema lead to?

Myxedema coma- high mortality rates

372

What is the drug of choice for hypothyroidism management?

levothyroxine

373

What is the MOA of levothyroxine?

Isomer of T4 is converted to T3

374

What are the ADRs of levothyroxine?

◦Arrhythmias
◦Tachycardia
◦Anginal pain
◦Cramps
◦HA
◦Restlessness
◦Sweating
◦Weight loss
◦Osteoporosis

375

What is the CI for levothyroxine?

Thyrotoxicosis

376

What how often do you need to be monitoring your pt if taking levthyroxine?

◦Every 6-8 weeks until TSH normalized, then every 6-12 months
◦If doses changed, recheck TSH in 2-3 months

377

Levothyroxine has many drug interactions. What does it alter absorption of?

◦Cholestyramine
◦Ferrous sulfate
◦Sucralfate
Aluminum hydroxide

378

Levothyroxine has many drug interactions. What does it incease the metabolism of?

◦Rifampin
◦Phenytoin
◦Carbamazepine

379

What is the effect of oral contraceptives or estrogen with levo?

◦Increase thyroid binding globulin, resulting in lower free thyroid hormone

380

What is the effect of lithium with levo?

◦Inhibits synthesis and release of thyroid hormone

381

What is the effect of amiodarone with levo?

Block conversion T4 to T3

382

What is the effect of warfarin with levo?

Increases metabolism of clotting factors

383

What are the other 2 drug choices for hypothyroidism management?

Liothyronine sodium and liotrix

384

Why is liothyronine generally not used for maintenance?

therapy because of its short half-life and duration of action.

385

What are the indications for liothyronine?

–Initial therapy of myxedema (skin disorder) and myxedema coma
–Short-term suppression of TSH in patients undergoing surgery for thyroid cancer.
–Patients w/5’-deiodinase deficiency who cannot convert T4 to T3.

386

Is liotrix any more effective than levo?

No

387

What is the specific tx regime for myxedema coma?

◦IV bolus levothyroxine 300-500mcg
◦Maintenance 75-100 mcg IV until able to switch to PO
◦IV hydrocortisone 100mg q 8h until coexisting adrenal suppression is ruled out
◦Supportive therapy- ventillation, euglycemia, blood pressure, body temp maintained

388

What is the specific tx for congenital hypothyroidism?

◦Initial therapy within 45 days of birth at 10-15mcg/kg/d, associated with improved IQ’s in treated infants
◦Dose progressively decreased to typical adult dose beginning 11-20 years
- aggressive tx important for normal development!

389

How is hypothyroidism tx in pregnancy?

—Treatment: levothyroxine
◦20% requires dose increase during pregnancy/ decrease after
◦Typically require 36 mcg/day increase in dosage

390

What causes hyperthyroidism?

◦Overproduction of endogenous hormone
◦Exposure to excess endogenous hormone
◦Elevated free and total T3, T4 or both serum concentrations

391

What are the subclinical and clinical serum levels of TSH for diagnosis?

—Subclinical
◦TSH 13.2 mcg/dL

392

What are S/S of hyperthyroidism?

◦Nervousness
◦Anxiety
◦Palpitations
◦Increased basal metabolic rate (BMR)
◦Weight loss
◦Increased appetite
◦Increased body temp (heat intolerance)
◦Sweating
◦Fine Tremor
◦Tachycardia
◦Classical ophthalmic signs

393

What is the most common cause of hyperthyroidism?

Graves dz

394

What is graves dz?

Autoimmune syndrome that includes hyperthyroidism, diffuse thyroid enlargement, myxedema, thyroid acropachy

395

What forms against the thyroid cell?

IgG antibodies bind and activate the receptor

396

Why is TSH undetectable in graves?

From the negative feedback from elevated thyroid hormone- disproportionate increase in T3 compared to T4

397

What is the most common cause of hyperthyroidism in preggo?

Graves
Inappropriate production of hCG can cause subclinical or overt hyperthyroidism

398

What are common complications if hyperthyroidism is left untreated in the preggos?

◦Spontaneous abortion
◦Premature delivery
◦Low birth weight
◦Eclampsia

399

What is the drug of choice for tx graves in preggo?

PTU at the lowest effective dose

400

What is a thyroid storm?

Life threatening medical emergency characterized by ◦Severe thyrotoxicosis, high fever (often > 103 F), tachycardia, tachypnea, dehydration, delirium-coma, N/V, and diarrhea

401

What are the precipitating factors to a thyroid storm?

◦Infection, trauma, surgery radioactive iodine treatment, withdrawl from antithyroid drugs

402

How can you tx a thyroid storm?

◦Suppression of thyroid hormone formation and secretion
◦Anti-adrenergic therapy
◦Administration corticosteroids
◦Treatment of complications

403

What are the pharmacologic options for hyperthyroidism?

Thioamides, Iodines and iodine containing agents. Radioiodine, Lithium carbonate, Beta adrenergic antagonists, corticosteroids

404

What are the thioamides?

PTU- propylthiouracil
MMI- methimazole

405

What is the MOA of the thioamides?

Block thyroid hormone synthesis
PTU also inhibits DI which deiodinates peripheral T4 to T3

406

What are the indications for the thioamides?

◦Management of hyperthyroidism
◦Thyrotoxic crisis
◦In the preparation of patients for surgical subtotal thyroidectomy

407

Why might MMI be preferred?

Generally has fewer side effect and is 10x more potent than PTU, meaning it requires lower dosages

408

What are the most frequent ADRs of thioamides?

–Rash
–Arthralgia
–Myalgia
–Cholestatic jaundice
–Lymphadenopathy
–Drug fever
–Psychosis
–Alopecia

409

What are the most serious ADRs of the thioamides? When do they typically happen?

Within first 3 mo of therapy
–Arganulocytosis-must obtain baseline white blood cell count (stop if develop fever or sore throat)
–Hepatotoxicity-baseline white blood cell count (stop if pt. develops fever or sore throat)
–Vasculitis-drug induced lupus or anti-neutrophil

410

What can thioamides cause in excessive amounts over long periods of time?

Hypothyroidism and enlargement of the thyroid gland

411

What are indications for the iodines and iodine containing agents?

◦Preoperatively for thyroidectomy (7-14 days)
◦Used after RAI (3-7 days), to allow RAI to concentrate in thyroid

412

What are the CI for iodines?

Should not be given to breastfeeding women- can cause goiter in infants

413

How are the iodines administered?

Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole

414

Should you give iodines long term?

No- they loose effectiveness

415

What are the ADRs of the iodines?

◦Hypersensitivity rxn
◦HA
◦Lacrimation
◦Conjunctivitis
◦Laryngitis
◦Thyrotoxicosis in patients w/nontoxic goiter
◦Drug fever
◦Acneform rash
◦Metallic taste in mouth

416

When is radioiodine used?

For thyroid ablation in the management of hyperthyroidism

417

When is radioiodine the agent of choice?

Graves, toxic autonomous nodules, toxic multinodular goiters

418

What is the goal of radioiodine? MOA?

To destroy overactive thyroid cells
◦Taken up by other organs- organification only in thyroid
◦The ablative effect is exerted primarily through beta-particle emissions, which destroy thyroid tissue.

419

What is the major disadvantage to using radioiodine?

◦Hypothyroidism in most patients
◦Can not be used in pregnancy
◦Hypothyroid often occurs months-years after RAI
◦African Americans are most likely to be resistant to RAI (require multiple doses)

420

What is the MOA of lithium carbonate?

◦Lithium inhibits thyroidal incorporation of I- into thyroid gland which inhibits the secretion of thyroid hormones from follicular cells

421

What are the indications for lithium carbonate?

Offers no advantage over thioamide
Can be used for temporary control of thyrotoxicosis in pts allergic to thioamides and iodine

422

When are beta-adrenergic antagonists used in hyperthyroidism?

to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance

423

Is it a primary or adjunct therapy?

Adjunct! No effect on peripheral thyrotixicosis and therapeutic effect

424

Which corticosteroids can be used in hyperthyroidism?

—Dexamethasone
—Prednisone
—Methylprednisolone
—Hyrocortisone

425

What are the effects of the corticosteroids?

◦Decreases thyroid action
◦Decreases immune response in Grave’s disease
reduce T3

426

When are corticosteroids useful?

Thyroiditis and thyroid storm

427

When is a thyroidectomy indicated?

large glands, severe ophthalmopathy, lack of remission on treatment

428

What pts should not have a thyroidectomy?

On pts with low RAI uptake

429

What medications should the pt be on before during and after the surgery?

—Propylthiouracil (PTU) or methimazole (MMI) until pt is euthyroid (6-8 weeks) followed by iodide 500 mg/day x 10-14 days
—Beta blocker (propranolol/ nadolol) pre- and post-surgery to maintain HR

430

What are complications of a thyroidectomy?

◦Hyperthyroidism
◦Hypothyroidism
◦Hypoparathyroidism
◦Vocal cord abnormalities

431

What are drugs your pt may be taking that if you added a thyroid or antithyroid agent would have interactions?

◦Warfarin
◦Lithium
◦Diabetes medication requirements may change
◦Potassium iodide used as expectorants
◦Cardiac glycosides such as digoxin may require dosage adjustments
◦Amiodarone
CNS depressants

432

Amiodarone and iodinated contrast media can inhibit conversion of T4 to T3 in peripheral circulation and the pituitary gland. What are the levels and when do these happen?

–Iodinated Contrast
‭ ‬Reduction in levels in week 1
‭ ‬Return to normal by week 2
–Amiodarone
‭ ‬Transient elevation in TSH during first 3 months
‭ ‬Persistent FT4 elevations and reduced T3 in on-going therapy

433

What prescription drugs containing iodides can induce thyroid dz?

–Amiodarone
–Radiocontrast dye
–Povidone iodine
–Iodinated glycerol

434

What non-prescription drugs containing iodides can induce thyroid dz?

–Cough and cold
–Kelp
–Herbals
–Dietary supplements/ weight loss products

435

What is iodine induced hyperthyroidism called?

Jod-basedow dz

436

When does jod-b develop and how is it tx?

◦Develops within 3-8 weeks after exposure in up to 5% pts
◦Treatment with thioamides and beta blockers

437

What pts are at risk of developing iodine induced hypothyroidism?

Pts being tx with Amiodarone

438

How is iodine induced hypothyroidism tx?

levothyroxine replacement

439

What other drug can induce hypothyroidism? How is this tx?

Lithium- more like if tx >2ys
Tx: levo to reverse
◦Can spontaneously resolve without treatment
◦Stopping lithium does not always resolve symptoms or goiter
◦May require surgical intervention

440

When might interferon alpha induced thyroid dz present?

within 6-8 weeks of starting therapy or occur 6-23 months after start

441

How is IFNa induced dz tx?

Hypothyroidism resolves spontaneously within 2-3 months after stopping therapy in most patients- may take longer

442

What are the precipitating factors to a thyroid storm?

◦Infection, trauma, surgery radioactive iodine treatment, withdrawl from antithyroid drugs

443

How can you tx a thyroid storm?

◦Suppression of thyroid hormone formation and secretion
◦Anti-adrenergic therapy
◦Administration corticosteroids
◦Treatment of complications

444

What are the pharmacologic options for hyperthyroidism?

Thioamides, Iodines and iodine containing agents. Radioiodine, Lithium carbonate, Beta adrenergic antagonists, corticosteroids

445

What are the thioamides?

PTU- propylthiouracil
MMI- methimazole

446

What is the MOA of the thioamides?

Block thyroid hormone synthesis
PTU also inhibits DI which deiodinates peripheral T4 to T3

447

What are the indications for the thioamides?

◦Management of hyperthyroidism
◦Thyrotoxic crisis
◦In the preparation of patients for surgical subtotal thyroidectomy

448

Why might MMI be preferred?

Generally has fewer side effect and is 10x more potent than PTU, meaning it requires lower dosages

449

What are the most frequent ADRs of thioamides?

–Rash
–Arthralgia
–Myalgia
–Cholestatic jaundice
–Lymphadenopathy
–Drug fever
–Psychosis
–Alopecia

450

What are the most serious ADRs of the thioamides? When do they typically happen?

Within first 3 mo of therapy
–Arganulocytosis-must obtain baseline white blood cell count (stop if develop fever or sore throat)
–Hepatotoxicity-baseline white blood cell count (stop if pt. develops fever or sore throat)
–Vasculitis-drug induced lupus or anti-neutrophil

451

What can thioamides cause in excessive amounts over long periods of time?

Hypothyroidism and enlargement of the thyroid gland

452

What are indications for the iodines and iodine containing agents?

◦Preoperatively for thyroidectomy (7-14 days)
◦Used after RAI (3-7 days), to allow RAI to concentrate in thyroid

453

What are the CI for iodines?

Should not be given to breastfeeding women- can cause goiter in infants

454

How are the iodines administered?

Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole

455

Should you give iodines long term?

No- they loose effectiveness

456

What are the ADRs of the iodines?

◦Hypersensitivity rxn
◦HA
◦Lacrimation
◦Conjunctivitis
◦Laryngitis
◦Thyrotoxicosis in patients w/nontoxic goiter
◦Drug fever
◦Acneform rash
◦Metallic taste in mouth

457

When is radioiodine used?

For thyroid ablation in the management of hyperthyroidism

458

When is radioiodine the agent of choice?

Graves, toxic autonomous nodules, toxic multinodular goiters

459

What is the goal of radioiodine? MOA?

To destroy overactive thyroid cells
◦Taken up by other organs- organification only in thyroid
◦The ablative effect is exerted primarily through beta-particle emissions, which destroy thyroid tissue.

460

What is the major disadvantage to using radioiodine?

◦Hypothyroidism in most patients
◦Can not be used in pregnancy
◦Hypothyroid often occurs months-years after RAI
◦African Americans are most likely to be resistant to RAI (require multiple doses)

461

What is the MOA of lithium carbonate?

◦Lithium inhibits thyroidal incorporation of I- into thyroid gland which inhibits the secretion of thyroid hormones from follicular cells

462

What are the indications for lithium carbonate?

Offers no advantage over thioamide
Can be used for temporary control of thyrotoxicosis in pts allergic to thioamides and iodine

463

When are beta-adrenergic antagonists used in hyperthyroidism?

to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance

464

Is it a primary or adjunct therapy?

Adjunct! No effect on peripheral thyrotixicosis and therapeutic effect

465

Which corticosteroids can be used in hyperthyroidism?

—Dexamethasone
—Prednisone
—Methylprednisolone
—Hyrocortisone

466

What are the effects of the corticosteroids?

◦Decreases thyroid action
◦Decreases immune response in Grave’s disease
reduce T3

467

When are corticosteroids useful?

Thyroiditis and thyroid storm

468

When is a thyroidectomy indicated?

large glands, severe ophthalmopathy, lack of remission on treatment

469

What pts should not have a thyroidectomy?

On pts with low RAI uptake

470

What medications should the pt be on before during and after the surgery?

—Propylthiouracil (PTU) or methimazole (MMI) until pt is euthyroid (6-8 weeks) followed by iodide 500 mg/day x 10-14 days
—Beta blocker (propranolol/ nadolol) pre- and post-surgery to maintain HR

471

What are complications of a thyroidectomy?

◦Hyperthyroidism
◦Hypothyroidism
◦Hypoparathyroidism
◦Vocal cord abnormalities

472

What are drugs your pt may be taking that if you added a thyroid or antithyroid agent would have interactions?

◦Warfarin
◦Lithium
◦Diabetes medication requirements may change
◦Potassium iodide used as expectorants
◦Cardiac glycosides such as digoxin may require dosage adjustments
◦Amiodarone
CNS depressants

473

Amiodarone and iodinated contrast media can inhibit conversion of T4 to T3 in peripheral circulation and the pituitary gland. What are the levels and when do these happen?

–Iodinated Contrast
‭ ‬Reduction in levels in week 1
‭ ‬Return to normal by week 2
–Amiodarone
‭ ‬Transient elevation in TSH during first 3 months
‭ ‬Persistent FT4 elevations and reduced T3 in on-going therapy

474

What prescription drugs containing iodides can induce thyroid dz?

–Amiodarone
–Radiocontrast dye
–Povidone iodine
–Iodinated glycerol

475

What non-prescription drugs containing iodides can induce thyroid dz?

–Cough and cold
–Kelp
–Herbals
–Dietary supplements/ weight loss products

476

What is iodine induced hyperthyroidism called?

Jod-basedow dz

477

When does jod-b develop and how is it tx?

◦Develops within 3-8 weeks after exposure in up to 5% pts
◦Treatment with thioamides and beta blockers

478

What pts are at risk of developing iodine induced hypothyroidism?

Pts being tx with Amiodarone

479

How is iodine induced hypothyroidism tx?

levothyroxine replacement

480

What other drug can induce hypothyroidism? How is this tx?

Lithium- more like if tx >2ys
Tx: levo to reverse
◦Can spontaneously resolve without treatment
◦Stopping lithium does not always resolve symptoms or goiter
◦May require surgical intervention

481

When might interferon alpha induced thyroid dz present?

within 6-8 weeks of starting therapy or occur 6-23 months after start

482

How is IFNa induced dz tx?

Hypothyroidism resolves spontaneously within 2-3 months after stopping therapy in most patients- may take longer

483

What are indications for the iodines and iodine containing agents?

◦Preoperatively for thyroidectomy (7-14 days)
◦Used after RAI (3-7 days), to allow RAI to concentrate in thyroid

484

What are the CI for iodines?

Should not be given to breastfeeding women- can cause goiter in infants

485

How are the iodines administered?

Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole

486

Should you give iodines long term?

No- they loose effectiveness

487

What are the ADRs of the iodines?

◦Hypersensitivity rxn
◦HA
◦Lacrimation
◦Conjunctivitis
◦Laryngitis
◦Thyrotoxicosis in patients w/nontoxic goiter
◦Drug fever
◦Acneform rash
◦Metallic taste in mouth

488

When is radioiodine used?

For thyroid ablation in the management of hyperthyroidism

489

When is radioiodine the agent of choice?

Graves, toxic autonomous nodules, toxic multinodular goiters

490

What is the goal of radioiodine? MOA?

To destroy overactive thyroid cells
◦Taken up by other organs- organification only in thyroid
◦The ablative effect is exerted primarily through beta-particle emissions, which destroy thyroid tissue.

491

What is the major disadvantage to using radioiodine?

◦Hypothyroidism in most patients
◦Can not be used in pregnancy
◦Hypothyroid often occurs months-years after RAI
◦African Americans are most likely to be resistant to RAI (require multiple doses)

492

What is the MOA of lithium carbonate?

◦Lithium inhibits thyroidal incorporation of I- into thyroid gland which inhibits the secretion of thyroid hormones from follicular cells

493

What are the indications for lithium carbonate?

Offers no advantage over thioamide
Can be used for temporary control of thyrotoxicosis in pts allergic to thioamides and iodine

494

When are beta-adrenergic antagonists used in hyperthyroidism?

to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance

495

Is it a primary or adjunct therapy?

Adjunct! No effect on peripheral thyrotixicosis and therapeutic effect

496

Which corticosteroids can be used in hyperthyroidism?

—Dexamethasone
—Prednisone
—Methylprednisolone
—Hyrocortisone

497

What are the effects of the corticosteroids?

◦Decreases thyroid action
◦Decreases immune response in Grave’s disease
reduce T3

498

When are corticosteroids useful?

Thyroiditis and thyroid storm

499

When is a thyroidectomy indicated?

large glands, severe ophthalmopathy, lack of remission on treatment

500

What pts should not have a thyroidectomy?

On pts with low RAI uptake